Langerhans Cell Histiocytosis (LCH)Phase 2NCT07022834
Real-world Study of Darafenib or Trametinib and Clofarabine for High-risk/Recurrent/Refractory Langerhans Cell Histiocytosis in Children
A Phase 2 study testing Dabrafenib or Trametinib and Clofarabine in people with Langerhans Cell Histiocytosis (LCH), run by West China Second University Hospital at 1 site in China.
Trial summary
Langerhans cell histiocytosis (LCH) is the most common histiocytosis in children, with an incidence of 2.6-8.9 per million. It is an inflammatory myeloid tumor with varied symptoms. Mild cases often resolve spontaneously, while severe cases can affect multiple organs and be life-threatening. Read more about this study
- Who is it for?
- Ages 0 to 18 years
- Conditions the study is for
- Langerhans Cell Histiocytosis (LCH)
- What is being tested?
- Dabrafenib or Trametinib and Clofarabine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteChina
- Study dates
- 1 Jun 2025to 1 Jun 2030
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 0 to 18 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Children aged 0-18 with LCH (CD1a+/CD207+);
- Initial LCH diagnosis with hematopoietic, liver, or spleen involvement;
- LCH patients with disease progression or reactivation after chemotherapy (e.g., prednisone, vincristine, cytarabine, clarithromycin) or targeted therapy;
- Consent to treatment and follow-up;
- ECOG score ≥ 2, Lansky score ≥ 50, organ function suitable for chemotherapy.
Who cannot join
- Other underlying diseases (e.g., primary immunodeficiency, heart/kidney failure, hepatitis, HIV, organ transplant);
- Secondary tumor;
- Recent chemotherapy, radiotherapy, or MAPK inhibitor use with lingering adverse effects;
- Ongoing nephrotoxic drug use;
- Refusal to consent.
- Exit Criteria:
Show all 9Show fewer
- Allergies to dabrafenib or trametinib and clofarabine；
- Disease progression after 3 months on dabrafenib or trametinib；
- Severe toxic side effects from clofarabine (grade 4 non-infectious non-hematological toxicity, SIRS, capillary leak syndrome)； 4）The doctor recommends halting the current treatment plan for the patient's benefit.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Xia Guo, MD contact
China1 site, 1 recruiting
- Recruiting
Department of Pediatric Hematology and Oncology, West China Second University Hospital, Sichuan University, Chengdu, China
Chengdu, Sichuan, 610041
Xue Tang, MD, 86+18280145819, txily0912@1226.com
About this study
Official title: A Real-world Investigation of the Combination of Darafenib or Trametinib and Clofarabine in the Treatment of High-risk, Recurrent, or Refractory Pediatric Patients With Langerhans Cell Histiocytosis.
Langerhans cell histiocytosis (LCH) is the most common histiocytosis in children, with an incidence of 2.6-8.9 per million. It is an inflammatory myeloid tumor with varied symptoms. Mild cases often resolve spontaneously, while severe cases can affect multiple organs and be life-threatening. LCH affecting the liver, spleen, or hematopoietic system has a poor prognosis and is high-risk group. The LCH-III study showed that low-risk children respond well to prednisone and vinblastine, with nearly 100% survival, but high-risk children's survival is about 80%, with a 30% reactivation rate.Long-term studies reveal that about 50% of patients are resistant to prednisone and vinblastine, leading to progression and recurrence.
Except combination of prednisone and vinblastine, cladribine (introduced in 1998) and MAPK inhibitors (introduced in 2014), have lowered the mortality rate of LCH in children. Cladribine, a nucleoside analogue, is used for treating recurrent acute myeloid leukemia in children by disrupting DNA synthesis. In the LCH-98-S regimen, low-risk children with LCH responded well to moderate doses of cladribine, but 44% of high-risk children still faced disease progression. Later studies showed that high-dose cladribine with medium-dose cytarabine increased survival in refractory LCH from 30% to 85%, but also raised chemotherapy toxicity, with some cases experiencing severe hematological toxicity and half of the deaths resulting from chemotherapy complications. Clofarabine, a nucleoside analogue, inhibits ribonucleotide reductase and DNA polymerase, offering stronger anti-tumor effects and fewer side effects than cladribine and fludarabine in treating refractory leukemia. Case reports show that LCH patients unresponsive to cladribine improve with clofarabine treatment at moderate doses (25mg/m2/day). A retrospective study of 58 LCH patients using clofarabine (25mg/m2/day) showed an 87% progression-free survival rate after one year. While the main side effect was grade 3 or higher hematological toxicity, 98.3% of patients tolerated it and completed treatment. Further prospective studies are needed to determine the optimal dose, duration, long-term efficacy, and complications of clofarabine in children with LCH.
Read more
Research indicates that childhood LCH is often linked to mutations in MAPK pathway genes, with over half of cases involving BRAFV600E mutations. MAPK inhibitors, like vemurafenib, dabrafenib and trametinib, are effective for relapsed and refractory LCH, but they don't eliminate malignant clones, leading to disease reactivation after stopping treatment. Some BRAF-deficient mutation LCH patients resist vemurafenib and dabrafenib, but trametinib can manage the disease in these cases. Activation of the MAPK pathway increases BCL2L1 expression in LCH cells, and rapamycin fails to induce apoptosis in BRAFV600E+ LCH cells, enhancing resistance to cell death. MAPK inhibitors combined with chemotherapy are theoretically more effective at inducing apoptosis in LCH cells and resetting the immune environment to eliminate malignant clones. Two clinical studies confirm their safety and efficacy in treating refractory recurrent LCH. In a follow-up of 10 LCH cases treated with nucleotide analogues and MAPK inhibitors, only 2 patients relapsed after a short treatment duration. Additionally, 19 children with BRAFV600E mutation LCH were treated with cladribine, cytarabine, and vemurafenib, achieving a 100% response rate. Nearly 80% completed treatment without recurrence, and no increase in side effects was observed.
Since 2020, our center treated nearly 40 LCH patients with MAPK inhibitors, including 14 combined with LCH-III chemotherapy. Follow-ups show no severe toxic side effects, aligning with literature. However, most high-risk patients, especially those who stopped oral MAPK inhibitors, had disease reactivation. Two high-risk patients with liver involvement achieved complete liver lesion regression with cladribine. This clinical study aims to assess the efficacy and safety of dabrafenib or trametinib and clofarabine for high-risk/recurrent/refractory LCH in children.
- Conditions
- Langerhans Cell Histiocytosis (LCH)
- Being tested
- Dabrafenib or Trametinib and Clofarabine
- Medical subject headings
- Histiocytosis, Langerhans-Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Dabrafenib or Trametinib and ClofarabineDrug
Drug: Dabrafenib or Trametinib Dabrafenib: 3-5 mg/kg/day; Trametinib: 0.025mg/kg/day
Drug: Clofarabine Consolidation therapy: 25 mg/m2/d, days 1-5 Maintenance therapy: 25 mg/m2/d, days 1-2
| Study group | Role | What they receive |
|---|---|---|
| Dabrafenib or Trametinib and Clofarabine | Experimental | Not described Receives: Drug: Dabrafenib or Trametinib and Clofarabine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression Free Survival
Measured: 24 months
Secondary outcomes (2)
Overall Response Rates
Measured: 3 months
Nature and Severity of Adverse Events
Measured: 18 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Jun 2025
- Study start1 Jun 2025
- Primary completion1 Jun 2028 (estimated)
- Study completion1 Jun 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (17)Papers the sponsor has linked to this study.
- Other trials for Langerhans Cell Histiocytosis (LCH)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- West China Second University Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Ju Gao, West China Second University Hospital
- Investigators
- Ju Gao, MD, Study chair, West China Second University Hospital, Sichuan University, Sichuan, China
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07022834
- Sponsor's protocol ID
- WCSH-LCH-2025
- Status last verified
- Jun 2025
- First submitted
- 7 Jun 2025
- Last updated
- 15 Jun 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Patient's clinical data, treatment , treatment evaluation response, and follow-up results
Publications
Evseev D, Osipova D, Kalinina I, Raykina E, Ignatova A, Lyudovskikh E, Baidildina D, Popov A, Zhogov V, Semchenkova A, Litvin E, Kotskaya N, Cherniak E, Voronin K, Burtsev E, Bronin G, Vlasova I, Purbueva B, Fink O, Pristanskova E, Dzhukaeva I, Erega E, Novichkova G, Maschan A, Maschan M. Vemurafenib combined with cladribine and cytarabine results in durable remission of pediatric BRAF V600E-positive LCH. Blood Adv. 2023 Sep 26;7(18):5246-5257. doi: 10.1182/bloodadvances.2022009067.
PubMed 37216396Karri V, Lin H, Velazquez J, Batajoo A, Parekh D, Stanton W, Abhyankar H, El-Mallawany NK, Agrusa J, Eckstein O, Gulati N, Schwartz J, Woods-Swafford W, Boyd J, Saha A, Allen CE, McClain KL. Clinical, radiological and molecular responses to combination chemotherapy with MAPK pathway inhibition in relapsed and refractory Langerhans cell histiocytosis. Br J Haematol. 2024 May;204(5):1882-1887. doi: 10.1111/bjh.19380. Epub 2024 Mar 19.
PubMed 38501390Bigenwald C, Le Berichel J, Wilk CM, Chakraborty R, Chen ST, Tabachnikova A, Mancusi R, Abhyankar H, Casanova-Acebes M, Laface I, Akturk G, Jobson J, Karoulia Z, Martin JC, Grout J, Rafiei A, Lin H, Manz MG, Baccarini A, Poulikakos PI, Brown BD, Gnjatic S, Lujambio A, McClain KL, Picarsic J, Allen CE, Merad M. BRAFV600E-induced senescence drives Langerhans cell histiocytosis pathophysiology. Nat Med. 2021 May;27(5):851-861. doi: 10.1038/s41591-021-01304-x. Epub 2021 May 6.
PubMed 33958797Hogstad B, Berres ML, Chakraborty R, Tang J, Bigenwald C, Serasinghe M, Lim KPH, Lin H, Man TK, Remark R, Baxter S, Kana V, Jordan S, Karoulia Z, Kwan WH, Leboeuf M, Brandt E, Salmon H, McClain K, Poulikakos P, Chipuk J, Mulder WJM, Allen CE, Merad M. RAF/MEK/extracellular signal-related kinase pathway suppresses dendritic cell migration and traps dendritic cells in Langerhans cell histiocytosis lesions. J Exp Med. 2018 Jan 2;215(1):319-336. doi: 10.1084/jem.20161881. Epub 2017 Dec 20.
PubMed 29263218Lin HT, Wikenheiser-Brokamp KA, Udstuen G, Jones B, McCormack FX. Marked Improvement in Soft Tissue and CNS Manifestations of Adult Langerhans Cell Histiocytosis on Targeted MEK Inhibitor Therapy. Chest. 2023 Feb;163(2):e53-e56. doi: 10.1016/j.chest.2022.10.003.
PubMed 36759117Whitlock JA, Geoerger B, Dunkel IJ, Roughton M, Choi J, Osterloh L, Russo M, Hargrave D. Dabrafenib, alone or in combination with trametinib, in BRAF V600-mutated pediatric Langerhans cell histiocytosis. Blood Adv. 2023 Aug 8;7(15):3806-3815. doi: 10.1182/bloodadvances.2022008414.
PubMed 36884302Cournoyer E, Ferrell J, Sharp S, Ray A, Jordan M, Dandoy C, Grimley M, Roy S, Lorsbach R, Merrow AC, Nelson A, Bartlett A, Picarsic J, Kumar A. Dabrafenib and trametinib in Langerhans cell histiocytosis and other histiocytic disorders. Haematologica. 2024 Apr 1;109(4):1137-1148. doi: 10.3324/haematol.2023.283295.
PubMed 37731389Donadieu J, Larabi IA, Tardieu M, Visser J, Hutter C, Sieni E, Kabbara N, Barkaoui M, Miron J, Chalard F, Milne P, Haroche J, Cohen F, Helias-Rodzewicz Z, Simon N, Jehanne M, Kolenova A, Pagnier A, Aladjidi N, Schneider P, Plat G, Lutun A, Sonntagbauer A, Lehrnbecher T, Ferster A, Efremova V, Ahlmann M, Blanc L, Nicholson J, Lambilliote A, Boudiaf H, Lissat A, Svojgr K, Bernard F, Elitzur S, Golan M, Evseev D, Maschan M, Idbaih A, Slater O, Minkov M, Taly V, Collin M, Alvarez JC, Emile JF, Heritier S. Vemurafenib for Refractory Multisystem Langerhans Cell Histiocytosis in Children: An International Observational Study. J Clin Oncol. 2019 Nov 1;37(31):2857-2865. doi: 10.1200/JCO.19.00456. Epub 2019 Sep 12.
PubMed 31513482Abraham A, Alsultan A, Jeng M, Rodriguez-Galindo C, Campbell PK. Clofarabine salvage therapy for refractory high-risk langerhans cell histiocytosis. Pediatr Blood Cancer. 2013 Jun;60(6):E19-22. doi: 10.1002/pbc.24436. Epub 2012 Dec 19.
PubMed 23255383Rodriguez-Galindo C, Jeng M, Khuu P, McCarville MB, Jeha S. Clofarabine in refractory Langerhans cell histiocytosis. Pediatr Blood Cancer. 2008 Nov;51(5):703-6. doi: 10.1002/pbc.21668.
PubMed 18623218Donadieu J, Bernard F, van Noesel M, Barkaoui M, Bardet O, Mura R, Arico M, Piguet C, Gandemer V, Armari Alla C, Clausen N, Jeziorski E, Lambilliote A, Weitzman S, Henter JI, Van Den Bos C; Salvage Group of the Histiocyte Society. Cladribine and cytarabine in refractory multisystem Langerhans cell histiocytosis: results of an international phase 2 study. Blood. 2015 Sep 17;126(12):1415-23. doi: 10.1182/blood-2015-03-635151. Epub 2015 Jul 20.
PubMed 26194764Weitzman S, Braier J, Donadieu J, Egeler RM, Grois N, Ladisch S, Potschger U, Webb D, Whitlock J, Arceci RJ. 2'-Chlorodeoxyadenosine (2-CdA) as salvage therapy for Langerhans cell histiocytosis (LCH). results of the LCH-S-98 protocol of the Histiocyte Society. Pediatr Blood Cancer. 2009 Dec 15;53(7):1271-6. doi: 10.1002/pbc.22229.
PubMed 19731321Thalhammer J, Jeziorski E, Marec-Berard P, Barkaoui MA, Pagnier A, Rohrlich PS, Chevallier A, Carausu L, Aladjidi N, Rigaud C, Leruste A, Azarnoush S, Lauvray T, Le Louet S, Gandemer V, Treguier P, Mansuy L, Pasquet M, Olivier L, Rome A, Saultier P, Isfan F, Renard C, Li Thiao Te V, Salmon A, Blanc L, Abou Chahla W, Lambilliotte A, Stephan JL, Geissmann F, Lejeune J, Mallebranche C, Reguerre Y, Grain A, Thomas C, Helias-Rodzewicz Z, Moshous D, Fenneteau O, Coulomb-L'Hermine A, Lapillonne H, de Saint-Basile G, Emile JF, Heritier S, Donadieu J. Childhood Langerhans cell histiocytosis hematological involvement: severity associated with BRAFV600E loads. Blood. 2025 Mar 6;145(10):1061-1073. doi: 10.1182/blood.2024025625.
PubMed 39486044Haupt R, Nanduri V, Calevo MG, Bernstrand C, Braier JL, Broadbent V, Rey G, McClain KL, Janka-Schaub G, Egeler RM. Permanent consequences in Langerhans cell histiocytosis patients: a pilot study from the Histiocyte Society-Late Effects Study Group. Pediatr Blood Cancer. 2004 May;42(5):438-44. doi: 10.1002/pbc.20021.
PubMed 15049016Parekh D, Lin H, Batajoo A, Peckham-Gregory E, Karri V, Stanton W, Scull B, Fleishmann R, El-Mallawany N, Eckstein OS, Prudowsky ZD, Gulati N, Agrusa JE, Ahmed AZ, Chu R, Dietz MS, Goldman SC, Hogarty MD, Imran H, Intzes S, Kim JM, Kopp LM, Levy CF, Neff P, Pillai PM, Sisk BA, Schiff DE, Trobaugh-Lotrario AD, Walkovich K, McClain KL, Allen CE. Clofarabine monotherapy in aggressive, relapsed and refractory Langerhans cell histiocytosis. Br J Haematol. 2024 May;204(5):1888-1893. doi: 10.1111/bjh.19376. Epub 2024 Mar 19.
PubMed 38501389
Study at a glance
From the registry record, last updated by the sponsor on 15 Jun 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Real-world Investigation of the Combination of Darafenib or Trametinib and Clofarabine in the Treatment of High-risk, Recurrent, or Refractory Pediatric Patients With Langerhans Cell Histiocytosis.
- ClinicalTrials.gov ID
- NCT07022834
- Acronym / sponsor ID
- WCSH-LCH-2025
- Conditions
- Langerhans Cell Histiocytosis (LCH)
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 20 participants (estimated)
- Lead sponsor
- West China Second University HospitalUniversity, hospital or other
- Study start
- 1 Jun 2025 (actual)
- Primary completion
- 1 Jun 2028 (estimated)
- Study completion
- 1 Jun 2030 (estimated)
- First posted
- 15 Jun 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Langerhans cell histiocytosis (LCH) is the most common histiocytosis in children, with an incidence of 2.6-8.9 per million. It is an inflammatory myeloid tumor with varied symptoms. Mild cases often resolve spontaneously, while severe cases can affect multiple organs and be life-threatening. LCH affecting the liver, spleen, or hematopoietic system has a poor prognosis and is high-risk group. The LCH-III study showed that low-risk children respond well to prednisone and vinblastine, with nearly 100% survival, but high-risk children's survival is about 80%, with a 30% reactivation rate.Long-term studies reveal that about 50% of patients are resistant to prednisone and vinblastine, leading to progression and recurrence.
Except combination of prednisone and vinblastine, cladribine (introduced in 1998) and MAPK inhibitors (introduced in 2014), have lowered the mortality rate of LCH in children. Cladribine, a nucleoside analogue, is used for treating recurrent acute myeloid leukemia in children by disrupting DNA synthesis. In the LCH-98-S regimen, low-risk children with LCH responded well to moderate doses of cladribine, but 44% of high-risk children still faced disease progression. Later studies showed that high-dose cladribine with medium-dose cytarabine increased survival in refractory LCH from 30% to 85%, but also raised chemotherapy toxicity, with some cases experiencing severe hematological toxicity and half of the deaths resulting from chemotherapy complications. Clofarabine, a nucleoside analogue, inhibits ribonucleotide reductase and DNA polymerase, offering stronger anti-tumor effects and fewer side effects than cladribine and fludarabine in treating refractory leukemia. Case reports show that LCH patients unresponsive to cladribine improve with clofarabine treatment at moderate doses (25mg/m2/day). A retrospective study of 58 LCH patients using clofarabine (25mg/m2/day) showed an 87% progression-free survival rate after one year. While the main side effect was grade 3 or higher hematological toxicity, 98.3% of patients tolerated it and completed treatment. Further prospective studies are needed to determine the optimal dose, duration, long-term efficacy, and complications of clofarabine in children with LCH.
Research indicates that childhood LCH is often linked to mutations in MAPK pathway genes, with over half of cases involving BRAFV600E mutations. MAPK inhibitors, like vemurafenib, dabrafenib and trametinib, are effective for relapsed and refractory LCH, but they don't eliminate malignant clones, leading to disease reactivation after stopping treatment. Some BRAF-deficient mutation LCH patients resist vemurafenib and dabrafenib, but trametinib can manage the disease in these cases. Activation of the MAPK pathway increases BCL2L1 expression in LCH cells, and rapamycin fails to induce apoptosis in BRAFV600E+ LCH cells, enhancing resistance to cell death. MAPK inhibitors combined with chemotherapy are theoretically more effective at inducing apoptosis in LCH cells and resetting the immune environment to eliminate malignant clones. Two clinical studies confirm their safety and efficacy in treating refractory recurrent LCH. In a follow-up of 10 LCH cases treated with nucleotide analogues and MAPK inhibitors, only 2 patients relapsed after a short treatment duration. Additionally, 19 children with BRAFV600E mutation LCH were treated with cladribine, cytarabine, and vemurafenib, achieving a 100% response rate. Nearly 80% completed treatment without recurrence, and no increase in side effects was observed.
Since 2020, our center treated nearly 40 LCH patients with MAPK inhibitors, including 14 combined with LCH-III chemotherapy. Follow-ups show no severe toxic side effects, aligning with literature. However, most high-risk patients, especially those who stopped oral MAPK inhibitors, had disease reactivation. Two high-risk patients with liver involvement achieved complete liver lesion regression with cladribine. This clinical study aims to assess the efficacy and safety of dabrafenib or trametinib and clofarabine for high-risk/recurrent/refractory LCH in children.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Dabrafenib or Trametinib and Clofarabine | Experimental | Drug: Dabrafenib or Trametinib and Clofarabine |
Who may qualify
- Ages
- 0 to 18 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (5 listed)
- Children aged 0-18 with LCH (CD1a+/CD207+);
- Initial LCH diagnosis with hematopoietic, liver, or spleen involvement;
- LCH patients with disease progression or reactivation after chemotherapy (e.g., prednisone, vincristine, cytarabine, clarithromycin) or targeted therapy;
- Consent to treatment and follow-up;
- ECOG score ≥ 2, Lansky score ≥ 50, organ function suitable for chemotherapy.
Key exclusion criteria (9 listed)
- Other underlying diseases (e.g., primary immunodeficiency, heart/kidney failure, hepatitis, HIV, organ transplant);
- Secondary tumor;
- Recent chemotherapy, radiotherapy, or MAPK inhibitor use with lingering adverse effects;
- Ongoing nephrotoxic drug use;
- Refusal to consent.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Dabrafenib or Trametinib and ClofarabineDrug: Dabrafenib or Trametinib Dabrafenib: 3-5 mg/kg/day; Trametinib: 0.025mg/kg/day Drug: Clofarabine Consolidation therapy: 25 mg/m2/d, days 1-5 Maintenance therapy: 25 mg/m2/d, days 1-2 | Drug | Dabrafenib or Trametinib and Clofarabine |
Primary outcome
Progression Free Survival
Time frame: 24 months
2 secondary outcomes
Overall Response Rates
Time frame: 3 months
Nature and Severity of Adverse Events
Time frame: 18 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Jun 2025.
- Results publication: PubMed 37216396Evseev D, Osipova D, Kalinina I, Raykina E, Ignatova A, Lyudovskikh E, Baidildina D, Popov A, Zhogov V, Semchenkova A, Litvin E, Kotskaya N, Cherniak E, Voronin K, Burtsev E, Bronin G, Vlasova I, Purbueva B, Fink O, Pristanskova E, Dzhukaeva I, Erega E, Novichkova G, Maschan A, Maschan M. Vemurafenib combined with cladribine and cytarabine results in durable remission of pediatric BRAF V600E-positive LCH. Blood Adv. 2023 Sep 26;7(18):5246-5257. doi: 10.1182/bloodadvances.2022009067.
- Results publication: PubMed 38501390Karri V, Lin H, Velazquez J, Batajoo A, Parekh D, Stanton W, Abhyankar H, El-Mallawany NK, Agrusa J, Eckstein O, Gulati N, Schwartz J, Woods-Swafford W, Boyd J, Saha A, Allen CE, McClain KL. Clinical, radiological and molecular responses to combination chemotherapy with MAPK pathway inhibition in relapsed and refractory Langerhans cell histiocytosis. Br J Haematol. 2024 May;204(5):1882-1887. doi: 10.1111/bjh.19380. Epub 2024 Mar 19.
- Results publication: PubMed 33958797Bigenwald C, Le Berichel J, Wilk CM, Chakraborty R, Chen ST, Tabachnikova A, Mancusi R, Abhyankar H, Casanova-Acebes M, Laface I, Akturk G, Jobson J, Karoulia Z, Martin JC, Grout J, Rafiei A, Lin H, Manz MG, Baccarini A, Poulikakos PI, Brown BD, Gnjatic S, Lujambio A, McClain KL, Picarsic J, Allen CE, Merad M. BRAFV600E-induced senescence drives Langerhans cell histiocytosis pathophysiology. Nat Med. 2021 May;27(5):851-861. doi: 10.1038/s41591-021-01304-x. Epub 2021 May 6.
- Results publication: PubMed 29263218Hogstad B, Berres ML, Chakraborty R, Tang J, Bigenwald C, Serasinghe M, Lim KPH, Lin H, Man TK, Remark R, Baxter S, Kana V, Jordan S, Karoulia Z, Kwan WH, Leboeuf M, Brandt E, Salmon H, McClain K, Poulikakos P, Chipuk J, Mulder WJM, Allen CE, Merad M. RAF/MEK/extracellular signal-related kinase pathway suppresses dendritic cell migration and traps dendritic cells in Langerhans cell histiocytosis lesions. J Exp Med. 2018 Jan 2;215(1):319-336. doi: 10.1084/jem.20161881. Epub 2017 Dec 20.
- Results publication: PubMed 36759117Lin HT, Wikenheiser-Brokamp KA, Udstuen G, Jones B, McCormack FX. Marked Improvement in Soft Tissue and CNS Manifestations of Adult Langerhans Cell Histiocytosis on Targeted MEK Inhibitor Therapy. Chest. 2023 Feb;163(2):e53-e56. doi: 10.1016/j.chest.2022.10.003.
- Results publication: PubMed 36884302Whitlock JA, Geoerger B, Dunkel IJ, Roughton M, Choi J, Osterloh L, Russo M, Hargrave D. Dabrafenib, alone or in combination with trametinib, in BRAF V600-mutated pediatric Langerhans cell histiocytosis. Blood Adv. 2023 Aug 8;7(15):3806-3815. doi: 10.1182/bloodadvances.2022008414.
- Results publication: PubMed 37731389Cournoyer E, Ferrell J, Sharp S, Ray A, Jordan M, Dandoy C, Grimley M, Roy S, Lorsbach R, Merrow AC, Nelson A, Bartlett A, Picarsic J, Kumar A. Dabrafenib and trametinib in Langerhans cell histiocytosis and other histiocytic disorders. Haematologica. 2024 Apr 1;109(4):1137-1148. doi: 10.3324/haematol.2023.283295.
- Results publication: PubMed 31513482Donadieu J, Larabi IA, Tardieu M, Visser J, Hutter C, Sieni E, Kabbara N, Barkaoui M, Miron J, Chalard F, Milne P, Haroche J, Cohen F, Helias-Rodzewicz Z, Simon N, Jehanne M, Kolenova A, Pagnier A, Aladjidi N, Schneider P, Plat G, Lutun A, Sonntagbauer A, Lehrnbecher T, Ferster A, Efremova V, Ahlmann M, Blanc L, Nicholson J, Lambilliote A, Boudiaf H, Lissat A, Svojgr K, Bernard F, Elitzur S, Golan M, Evseev D, Maschan M, Idbaih A, Slater O, Minkov M, Taly V, Collin M, Alvarez JC, Emile JF, Heritier S. Vemurafenib for Refractory Multisystem Langerhans Cell Histiocytosis in Children: An International Observational Study. J Clin Oncol. 2019 Nov 1;37(31):2857-2865. doi: 10.1200/JCO.19.00456. Epub 2019 Sep 12.
- Results publication: PubMed 23255383Abraham A, Alsultan A, Jeng M, Rodriguez-Galindo C, Campbell PK. Clofarabine salvage therapy for refractory high-risk langerhans cell histiocytosis. Pediatr Blood Cancer. 2013 Jun;60(6):E19-22. doi: 10.1002/pbc.24436. Epub 2012 Dec 19.
- Results publication: PubMed 18623218Rodriguez-Galindo C, Jeng M, Khuu P, McCarville MB, Jeha S. Clofarabine in refractory Langerhans cell histiocytosis. Pediatr Blood Cancer. 2008 Nov;51(5):703-6. doi: 10.1002/pbc.21668.
- Results publication: PubMed 26194764Donadieu J, Bernard F, van Noesel M, Barkaoui M, Bardet O, Mura R, Arico M, Piguet C, Gandemer V, Armari Alla C, Clausen N, Jeziorski E, Lambilliote A, Weitzman S, Henter JI, Van Den Bos C; Salvage Group of the Histiocyte Society. Cladribine and cytarabine in refractory multisystem Langerhans cell histiocytosis: results of an international phase 2 study. Blood. 2015 Sep 17;126(12):1415-23. doi: 10.1182/blood-2015-03-635151. Epub 2015 Jul 20.
- Results publication: PubMed 19731321Weitzman S, Braier J, Donadieu J, Egeler RM, Grois N, Ladisch S, Potschger U, Webb D, Whitlock J, Arceci RJ. 2'-Chlorodeoxyadenosine (2-CdA) as salvage therapy for Langerhans cell histiocytosis (LCH). results of the LCH-S-98 protocol of the Histiocyte Society. Pediatr Blood Cancer. 2009 Dec 15;53(7):1271-6. doi: 10.1002/pbc.22229.
- Individual participant dataSharing planned: Yes. Patient's clinical data, treatment , treatment evaluation response, and follow-up results
Related trials for Langerhans Cell Histiocytosis (LCH)
RecruitingObservational study
Registry for Patients With Erdheim-Chester Disease and Other Histiocytoses
Erdheim-Chester Disease
RecruitingPhase 2
A Study With Tovorafenib (DAY101) as a Treatment Option for Progressive, Relapsed, or Refractory Langerhans Cell Histiocytosis
Recurrent Langerhans Cell Histiocytosis, Refractory Langerhans Cell Histiocytosis
Active, not recruitingPhase 2
Ensartinib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With ALK or ROS1 Genomic Alterations (A Pediatric MATCH Treatment Trial)
Advanced Malignant Solid Neoplasm, Malignant Solid Neoplasm
RecruitingPhase 2
Cobimetinib in Refractory Langerhans Cell Histiocytosis (LCH), and Other Histiocytic Disorders
Langerhan's Cell Histiocytosis, Juvenile Xanthogranuloma
Enrolling by invitationPhase 1/2
A Single-Arm,Multicenter Phase, Phase II Clinical Trial of Adebrelimab Combined With Trametinib in the Treatment of Refractory Recurrent Langerhans Cell Histiocytosis in Children and Adolescents
Histiocytosis,Langerhans-Cell
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Xia Guo, MD contact
Ju Gao, MD study chair
West China Second University Hospital, Sichuan University, Sichuan, China
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Dabrafenib or Trametinib and Clofarabine in people with Langerhans Cell Histiocytosis (LCH), run by West China Second University Hospital at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 15 Jun 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Xue Tang, MD (86+18280145819, txily0912@126.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Progression Free Survival (time frame: 24 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07022834, which also lists 17 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Jun 2025.